An individual's susceptibility to the damaging effect of his environment appears to be under the influence of genetic and other factors. Diseases arising from genetic-environmental interaction can be prevented if the inherited abnormality is detected prior to the injury and the environmental exposure avoided or modified. Alpha 1-antitrypsin deficiency (AATD) appears to predispose to chronic obstructive lung disease through this mechanism. Much evidence suggests that other inherited predisposing factors exist. This project seeks to clarify the mechanisms leading to lung damage in AATD and to uncover other predisposing factors. Such knowledge could lead to the developement of effective preventive medicine programs. Prospective studies of patients and presumably healthy subjects will be employed to clarify the clinical, pathological, physiological and biochemical defects in these states. Knowledge of the evolution and prognosis of these lung diseases will be useful in assessing the efficacy of any specific therapy. A survey of industrial workers employed in a polluted atmosphere will clarify the importance of AATD, other inherited predisposing factors and of screening programs to uncover early signs of lung dysfunction. In this population we will undertake an evaluation of the application of sputum cytology to the detection of early bronchitis.